Synthesis, characterization and antitumor activity of new ferrocene incorporated N,N′-disubstituted thioureas

Abstract

We report herein the synthesis, structural characterization and activity against human ovarian tumour models: A2780 (parent), A2780(cisR) (resistant to cisplatin) and A2780(ZD0473R) (resistant to the cisplatin analogue denoted as ZD0473) of two ferrocene incorporated N,N'-disubstituted thioureas {1-benzoyl-3-(4-ferrocenylphenyl)thiourea, B16, and 1-acetyl-3-(4-ferrocenylphenyl)thiourea, B3}. Structural characterization has been based on FT-IR, multinuclear ((1)H and (13)C) NMR, elemental analysis and single crystal X-ray diffractometry. Ferrocene-incorporated thioureas may present themselves as a new class of metal-based tumour active compounds. The cyclic voltammetric measurements indicate that B16 undergoes partial intercalation with the CT-DNA whereas B3 undergoes only electrostatic interaction with the same. Partial prevention of BamH1 digestion of pBR322 plasmid DNA that has been interacted with high concentrations of both B16 and B3 indicates that even non-covalent interactions can induce significant conformational changes in the DNA.

Thiourea Derivatives in Drug Design and Medicinal Chemistry: A Short Review

“…Phenyl derivative (R1=H, R2=Ph) of the series shows intercalation but methyl derivative shows electrostatic interaction. [41] Six novel ferrocenyl thioureas (R1=CH3, R2=CH3, -CH(CH3)2, -CH2C6H5, -CH2Cl, -C2H5, -C(CH3)3) were prepared, their DNA binding abilities and anti-oxidant properties were investigated. It was found that some compounds showed strong electrostatic interaction with DNA in its oxidized form rather than in reduced form.…”

Synthesis, structural characterization, DNA binding and antioxidant potency of new ferrocene incorporated acyl ureas

“…In this struggle tremendous attention has been given to the ferrocene and its derivatives. Ferrocene [2], nitrophenyl ferrocene [3], antimony derivatives of ferrocene [1] and thiourea [4] and selenourea derivatives of ferrocene [5][6][7] have been evaluated for their interactions with DNA. It has been observed that almost all the derivatives of ferrocene have higher drug-DNA binding constant than simple positively charged ferrocene moiety (3.45 x 10 2 M -1 ) although when these derivatives are not coupled with ferrocene then they are themselves less active for DNA.…”

Study of ferrocene derivatives Fe(C5H4X)(C5H5−n Y n ) by cyclic voltammetry and matrix-activated laser desorption/ionization time-of-flight mass spectrometry

“…It should be mentioned that the screening of the iron atom by two bulky ligands minimize the influence of the solva tion effects on the oxidation and reduction potentials of the substrates, which often results in the absence of a de pendence of the oxidation potential on the nature of the solvent used. Interest in ferrocene derivatives is due to their use in pharmacology, in particular, for the treatment of oncology, diabetes, malaria, and other infection dis eases 17, 18 and applications in petrochemistry 19 Ferrocene derivatives 2-9 were studied by CV in 1,2 di chloroethane containing Bu 4 NPF 6 as a supporting elec trolyte (Fig. 1).…”